A new in utero model for lateral facial clefts.
The etiopathogenesis behind the formation of atypical craniofacial facial clefts remains unknown. To test the hypothesis that physical restricting forces such as amniotic bands can lead to the formation of these unusual clefts in the postorganogenesis period, we have modified a previously reported fetal lamb model of amniotic band syndrome to examine the effects of these bands on craniofacial development. Five 70-day gestation fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. In each animal, an attempt was made to create a lateral craniofacial cleft by applying a 2-0 nylon suture as a constriction band to the growing face. The sutures were attached to either the zygomatic arch or the infraorbital rim externally and then looped circumferentially into the oral commissure. Each suture was positioned so as to create either a Tessier type 5 or a Tessier type 7 cleft. Four of five fetal lambs survived to term. Both types of lateral facial clefts were effectively produced using this model. In each group, the presence of an intraoral constriction band led to the formation of macrostomia, with an average 7.4-mm lateral displacement of the oral commissure. In addition to these soft tissue changes, each animal also had partial bony clefting (i.e., a bony groove) induced by the pressure of the restriction band across the growing facial skeleton. In the two lambs with the Tessier type 7 cleft, incomplete bony clefts developed across the zygomatic arch. In three animals with bands placed across the medial infraorbital rim, significant infraorbital and malar bony clefts formed similar to a classic Tessier type 5 facial cleft. No evidence of tissue necrosis, maceration, or ulceration was noted in any animal. These data present, for the first time, evidence that the constriction of craniofacial growth by external forces such as a swallowed amnionic band can lead to the development of lateral facial clefting involving both soft tissue and bony elements. These malformations are likely due to a combination of directly tethering normal tissue migration and an increase in local pressure, which produces cellular ischemia and apoptosis. Furthermore, our data demonstrate that these clefts can occur later in fetal development during a period of facial growth rather than during the period of primary facial morphogenesis.
Stelnicki
E J
EJ
Division of Plastic and Reconstructive Surgery, Washington University, St. Louis, MO, USA.
Hoffman
W Y
WY
Vanderwall
K
K
Harrison
M R
MR
Foster
R
R
Longaker
M T
MT
D000652:Amniotic Band Syndrome / Q000196:embryology*; D000818:Animals; D017209:Apoptosis; D001934:Branchial Region / Q000196:embryology*; D003251:Constriction, Pathologic / Q000196:embryology; D004195:Disease Models, Animal; D005147:Facial Bones / Q000196:embryology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008265:Macrostomia / Q000196:embryology*; D011247:Pregnancy; D012756:Sheep